Mapping of cosmic radiation dose in Croatia.

The Earth is continually bombarded by high-energy particles coming from the outer space and the sun. These particles, termed cosmic radiation, interact with nuclei of atmospheric constituents and decrease in intensity with depth in the atmosphere. Measurements of photon and gamma radiation, performed with a Radiameter at 1 m above the ground, indicated dose rates of 50-100 nSv/h. The neutron dose rate was measured with the CR-39 track etch detector calibrated by the CERN-EU high-energy Reference Field (CERF) facility. Correlation between neutron dose rates and altitudes at 36 sites was examined in order to obtain a significant positive correlation coefficient; the resulting linear regression enabled estimation of a neutron dose at particular altitude. The measured neutron dose rate in Osijek (altitude of 89 m, latitude of 45.31° N) was 110 nSv/h.

Measurements of neutron radiation in aircraft.

Radiation environment is a complex mixture of charged particles of the solar and galactic origin, as well as of secondary particles created in an interaction of galactic cosmic particles with the nuclei of the Earth's atmosphere. A radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. In order to measure a neutron component of the cosmic radiation, we investigated a few combinations of a track etch detector (CR-39, LR-115) with a plastic converter or boron foil. Detector calibration was performed on neutrons coming from the nuclear reactor, as well as in the CERN-EU high-energy Reference Field (CERF) facility. From November 2007 to September 2008, the neutron dose equivalent was measured by the track detectors during five aircraft flights, in the north geographical latitude from 21° to 58°; the respective average dose rate, determined by using the D-4 detector (CR-39/B), was H(n)=5.9 µSv/h. The photon dose rate, measured by the electronic dosimeter RAD-60 SE, had the average value of H(f)=1.4 µSv/h.

Radon anomaly in soil gas as an earthquake precursor.

The mechanical processes of earthquake preparation are always accompanied by deformations; afterwards, the complex short- or long-term precursory phenomena can appear. Anomalies of radon concentrations in soil gas are registered a few weeks or months before many earthquakes. Radon concentrations in soil gas were continuously measured by the LR-115 nuclear track detectors at site A (Osijek) during a 4-year period, as well as by the Barasol semiconductor detector at site B (Kasina) during 2 years. We investigated the influence of the meteorological parameters on the temporal radon variations, and we determined the equation of the multiple regression that enabled the reduction (deconvolution) of the radon variation caused by the barometric pressure, rainfall and temperature. The pre-earthquake radon anomalies at site A indicated 46% of the seismic events, on criterion M>or=3, R<200 km, and 21% at site B. Empirical equations between earthquake magnitude, epicenter distance and precursor time enabled estimation or prediction of an earthquake that will rise at the epicenter distance R from the monitoring site in expecting precursor time T.

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport.

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A320 and ATR40 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or 10B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb-Paris-Buenos Aires and reversely, when one measured non-neutron cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 microSv/h and the TLD dosimeter registered the dose equivalent of 75 microSv or the average dose rate of 2.7 microSv/h; the neutron dosimeter gave the dose rate of 2.4 microSv/h. In the same month, February 2005, a traveling to Japan (24-h-flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4microSv/h; the neutron dosimeter gave the dose rate of 2.5 microSv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude that the neutron component carried about 50% of the total dose, that was near other known data.

Cosmic radiation dose in aircraft--a neutron track etch detector.

Cosmic radiation bombards us at high altitude by ionizing particles. The radiation environment is a complex mixture of charged particles of solar and galactic origin, as well as of secondary particles produced in interaction of the galactic cosmic particles with the nuclei of atmosphere of the Earth. The radiation field at aircraft altitude consists of different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard ATR 42 and A 320 aircrafts (flight level of 8 and 11 km, respectively) was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter. The estimated occupational effective dose for the aircraft crew (A 320) working 500 h per year was 1.64 mSv. Other experiments, or dose rate measurements with the neutron dosimeter, consisting of LR-115 track detector and boron foil BN-1 or 10B converter, were performed on five intercontinental flights. Comparison of the dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level showed that the neutron component carried about 50% of the total dose. The dose rate measurements on the flights from the Middle Europe to the South and Middle America, then to Korea and Japan, showed that the flights over or near the equator region carried less dose rate; this was in accordance with the known geomagnetic latitude effect.

Effect of creatine on the pancreatic beta-cell.

We report on the stimulatory effect of creatine on insulin secretion and ATP concentration in MIN-6 beta-cells. The addition of creatine (5 mM) to MIN-6 cells in the presence of glucose (1-10 mM) elicited a significant (p<0.001) increase in insulin secretion, but no effect was demonstrated in the absence of glucose. The lack of effect of creatine in the absence of glucose suggests that creatine may act as a potentiator of insulin secretion rather than as an initiator. The potentiatory effect of creatine is specific for glucose since no effect was found in the presence of other known initiators of insulin secretion (K(+), 2-ketoisocaproic acid and tolbutamide). Cellular ATP content was markedly increased by glucose (1-15 mM). Creatine (5 and 10 mM) further increased the ATP level at all glucose concentrations, and the effect was observed even in the absence of glucose. The results from this study demonstrate the ability of creatine to increase insulin secretion only in the presence of glucose, while its effect on increased cellular ATP was independent of the presence of glucose. The mechanism whereby creatine potentiates insulin release is yet to be investigated. However, our data suggest possible unique interactions between creatine and the glucose-dependent insulin secretory pathway.

Structure-activity relationships of alloxan-like compounds derived from uric acid.

The diabetogenic activity of a range of alloxan-like compounds derived from uric acid has been investigated. The classes of derivatives were: 5-substituted-isouric acids; 4,5-disubstituted-4, 5-dihydrouric acids; 5-substituted-pseudouric acids; salts of dehydro-uramil hydrate; salts of dehydro-isouramil hydrate; alloxan derivatives. Compounds were tested by intravenous injection into rats and diabetogenic activity assessed by production of persistent hyperglycaemia and glycosuria. The only essential structural feature common to all active compounds was the presence of a quinonoid pyrimidine system or its hydrated equivalent. The presence of the five-membered ring of uric acid (or an opened form thereof) did not abolish and in some compounds enhanced diabetogenic activity.

Effects of dehydrouramil on protein phosphorylation and insulin secretion in rat islets of Langerhans.

Dehydrouramil hydrate hydrochloride (DHU), a stable analogue of alloxan, inhibited the phosphorylation of an endogenous protein of Mr 53,000 catalysed by a Ca2+-calmodulin-dependent protein kinase in extracts of islets of Langerhans. The concentration of DHU required for 50% inhibition was 0.09 mM. DHU did not inhibit islet cyclic AMP-dependent protein kinase and caused only slight inhibition of Ca2+-phospholipid-dependent protein kinase. Inhibition of Ca2+-calmodulin-dependent protein kinase was neither prevented nor reversed by dithiothreitol. DHU did not affect the ability of calmodulin to activate cyclic AMP phosphodiesterase. In intact islets, pre-exposure to DHU impaired the insulin-secretory response to glucose and blocked the potentiatory effect on insulin secretion of forskolin, an activator of adenylate cyclase, and of tetradecanoylphorbol acetate (TPA), an activator of Ca2+-phospholipid-dependent protein kinase. The increase in islet cyclic AMP elicited by forskolin was not affected by DHU. The data are consistent with the hypothesis that protein phosphorylation catalysed by a Ca2+-calmodulin-dependent protein kinase may play a central role in the regulation of insulin secretion.

Diabetogenic action of alloxan-like compounds: cytotoxic effects of 5-hydroxy-pseudouric acid and dehydrouramil hydrate hydrochloride on rat pancreatic beta cells.

The effects on islet morphology and blood glucose concentration of intravenous administration of alloxan to rats have been compared with those of two new diabetogenic agents, 5-hydroxy-pseudouric acid (5-HPUA) and dehydrouramil hydrate hydrochloride (DHU). Administration of alloxan (0.35 mmol/kg) caused a classical triphasic change in blood glucose characterised by initial hyperglycaemia, subsequent hypoglycaemia and a delayed persistent hyperglycaemia. In contrast, 5-HPUA and DHU elicited persistent hyperglycaemia as early as 30 min after administration. Morphological evidence for degranulation, pyknosis, necrosis and widening of pericapillary spaces was obtained with all three agents. However, both 5-HPUA and DHU elicit considerably more rapid and extensive changes than alloxan, with evidence for extensive pyknosis occurring as early as 15 min after administration of DHU and 5-HPUA compared with 24 h for alloxan. The more marked potency of DHU and 5-HPUA may be at least partially attributable to the greater stability of these agents compared with alloxan, since solutions of DHU or 5-HPUA kept for 15 min prior to administration retained full diabetogenic activity, whereas similar treatment of alloxan solution completely abolished its diabetogenic activity. Since both 5-HPUA and DHU are potential metabolites of uric acid, their marked diabetogenic potency raises the possibility of a role for uric acid metabolites in the pathogenesis of diabetes mellitus.

Diabetogenic action of alloxan-like compounds: the effect of dehydrouramil hydrate hydrochloride on isolated islets of Langerhans of the rat.

Dehydrouramil hydrate hydrochloride (DHU) is an analogue of alloxan which retains the in vivo diabetogenic activity of alloxan but, in contrast to alloxan, is stable in aqueous media at physiological pH. Using rat islets of Langerhans, we have studied the acute effects of DHU on B cell function. Glucose-stimulated insulin release was markedly inhibited by DHU, the concentration of DHU giving 50% inhibition (I50) was 1 mmol/l; this was lowered to 0.5 mmol/l when the islets were exposed to DHU for 5 min before elevation of glucose concentration. The basis for this change appeared to be a protective effect of glucose, since the inclusion of 3-0-methylglucose during re-incubation with DHU also attenuated the subsequent inhibition of glucose-stimulated insulin release. The inhibitory effect on glucose-stimulated insulin release of a 5-min exposure to DHU persisted throughout a subsequent 120-min period in the absence of DHU. DHU also inhibited insulin release stimulated by mannose (20 mmol/l) or by 2-ketoisocaproate (20 mmol/l) with I50 of 1 and 0.5 mmol/l respectively. Concentrations of DHU up to 1 mmol/l had no significant effect on islet glucose oxidation or ATP content; 5 mmol/l DHU did not affect the rate of glucose oxidation, but lowered the ATP content by 30% without pre-incubation and by 60% in islets pre-incubated for 5 min with DHU before addition of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidation of uric acid. 4. Synthesis, structure, and diabetogenic action of 5-imino-2,4,6(1H,3H,5H)-pyrimidinetrione salts and their alloxan-like covalent adducts.

Three synthetic routes to salts of 5-amino-5-hydroxy-2,4,6(1H,3H,5H)-pyrimidinetrione (10) are described. The key reactions involved acid-catalyzed cleavage of 5-amino-5-ureido-2,4,6(1H,3H,5H)-pyrimidinetrione (7), conversion of uramil (8) to dehydrouramil (9) and subsequent hydration, and the condensation of alloxan (5) with ammonium salts. The carbinol ammonium salt structure 10a was unambiguously established by X-ray crystallography. New alloxan-like compounds 7, 9, and 10 were evaluated for diabetogenic activity in rats. Compound 7 was inactive, whereas compounds 9 and 10 showed the highest activity comparable to that of streptozotocin (12).